Our bodies are made up of about 60 trillion cells. Each of those cells manufactures proteins. The kinds of proteins the cell makes, determine the cell's particular characteristics and create the characteristics of the entire body.
The instructions for making these proteins are stored in the DNA which is organized into chromosomes. Genetic differences (mutations) in that stored information establish our individual differences and lead to inherited diseases.
People who do not have fragile X syndrome, make FMRP (fragile X mental retardation protein) in some of their cells. Those cells that do make FMRP are regulated as to when they make it, so that it is present when needed in the places where it is needed.
A person with fragile X syndrome has a mutation in the FMR1 (fragile X mental retardation 1) gene in the DNA that makes up the X chromosome. That mutation causes the cell to methylate a regulatory region of the FMR1 gene. The methylation turns off the FMR1 gene. Since the gene is turned off, the person doesn't make FMRP. That lack of a specific protein triggers fragile X syndrome.
How is Fragile X Syndrome Inherited? It's in the DNA
Fragile X syndrome is not an infectious disease like the common cold, tuberculosis, or athlete's foot. Diseases like these are caused by viruses, bacteria, and fungi. Infectious diseases are often passed from one person to another through personal contact.
Fragile X syndrome is not caused by a problem with nutrition. A person's diet may contribute to heart disease, the formation of gallstones, or heartburn. Nutritional diseases are often caused by someone eating too much of or too little of a particular nutrient.
Instead, fragile X syndrome is transmitted from parent to child through the genetic information (DNA) that is present in the sperm and eggs. Trinucleotide repeat disorders
Many inherited diseases like sickle cell and hemophilia are caused by a single change in the genetic code in the DNA. It is as if there is a single typographical error in the instructions for how to make the protein.
Fragile X syndrome is not the result of a single change in a base. Instead it is known as a trinucleotide repeat disorder. This is because instead of a single error in the code, there is the multiplication of part of the genetic information.
In persons who do not have fragile X syndrome, there is a section of the DNA in the FMR1 gene which is normally repeated a few times. It has a sequence in which cytosine, guanine and guanine (CGG) are repeated in that order about 30 times. Someone with the premutation has 55-200 repeated CGG's in that part of the gene. Someone with the full mutation has 200-800 CGG repeats.
We have also learned that a variety of other diseases such as Huntington disease and Friedreich ataxia fall in this category of expansion diseases. As a result, research on any of these diseases contributes to the understanding of the others.
Mutations
Perhaps the most complicated part of the inheritance of Fragile X syndrome is that the FMR1 gene can be unstable, which leads to frequent changes (mutations).
Most genes have a very low rate of mutation. The majority of individuals who inherit a disease have at least one parent who is a carrier for that disease since new mutations are rare.
In contrast, once the FMR1 gene changes from stable (standard) to unstable (premutation), it has a high probability of mutating from one generation to the next. Thus, there can be a family with no history of Fragile X syndrome in which it suddenly appears in a number of offspring.
Since the FMR1 gene is on the X chromosome, and since it has a tendency to mutate once it has become a premutation, the patterns of inheritance for Fragile X syndrome are complex.
Causes of Fragile X Syndrome
The instructions for making these proteins are stored in the DNA which is organized into chromosomes. Genetic differences (mutations) in that stored information establish our individual differences and lead to inherited diseases.
People who do not have fragile X syndrome, make FMRP (fragile X mental retardation protein) in some of their cells. Those cells that do make FMRP are regulated as to when they make it, so that it is present when needed in the places where it is needed.
A person with fragile X syndrome has a mutation in the FMR1 (fragile X mental retardation 1) gene in the DNA that makes up the X chromosome. That mutation causes the cell to methylate a regulatory region of the FMR1 gene. The methylation turns off the FMR1 gene. Since the gene is turned off, the person doesn't make FMRP. That lack of a specific protein triggers fragile X syndrome.
How is Fragile X Syndrome Inherited?
Fragile X syndrome is not an infectious disease like the common cold, tuberculosis, or athlete's foot. Diseases like these are caused by viruses, bacteria, and fungi. Infectious diseases are often passed from one person to another through personal contact.
Fragile X syndrome is not caused by a problem with nutrition. A person's diet may contribute to heart disease, the formation of gallstones, or heartburn. Nutritional diseases are often caused by someone eating too much of or too little of a particular nutrient.
Instead, fragile X syndrome is transmitted from parent to child through the genetic information (DNA) that is present in the sperm and eggs.
Trinucleotide repeat disorders
Many inherited diseases like sickle cell and hemophilia are caused by a single change in the genetic code in the DNA. It is as if there is a single typographical error in the instructions for how to make the protein.
In persons who do not have fragile X syndrome, there is a section of the DNA in the FMR1 gene which is normally repeated a few times. It has a sequence in which cytosine, guanine and guanine (CGG) are repeated in that order about 30 times. Someone with the premutation has 55-200 repeated CGG's in that part of the gene. Someone with the full mutation has 200-800 CGG repeats.
We have also learned that a variety of other diseases such as Huntington disease and Friedreich ataxia fall in this category of expansion diseases. As a result, research on any of these diseases contributes to the understanding of the others.
Mutations
Perhaps the most complicated part of the inheritance of Fragile X syndrome is that the FMR1 gene can be unstable, which leads to frequent changes (mutations).
Most genes have a very low rate of mutation. The majority of individuals who inherit a disease have at least one parent who is a carrier for that disease since new mutations are rare.
In contrast, once the FMR1 gene changes from stable (standard) to unstable (premutation), it has a high probability of mutating from one generation to the next. Thus, there can be a family with no history of Fragile X syndrome in which it suddenly appears in a number of offspring.
Since the FMR1 gene is on the X chromosome, and since it has a tendency to mutate once it has become a premutation, the patterns of inheritance for Fragile X syndrome are complex.
Effects of Fragile X Syndrome --->